INTRODUCTION: Direct oral anticoagulants (DOACs) are used in patients with non-valvular atrial fibrillation (NVAF) to prevent complications such as embolic events. Poor adherence to DOACs increases the risk of these complications. This manuscript reviews the impact of once-daily (OD) vs twice-daily (BID) dosing regimens on adherence and persistence to the authorized DOACs (dabigatran, rivaroxaban, apixaban and edoxaban) in patients with NVAF, aiming to provide insights into guide clinical decision-making. METHODS: A systematic review was performed. First, a bibliographical search was carried out in PubMed, Scopus and the Cochrane Library. Articles that provided quantitative data comparing adherence and/or persistence associated with OD vs BID regimens of DOACs among patients receiving treatment for NVAF were included. Two analyses of adherence and persistence were conducted, one based on the overall outcomes and another, more restricted, to minimize the risk of overestimating results. Additionally, univariate analyses were conducted based on the number of follow-up days and the DOAC molecule. RESULTS: Thirty-nine studies, involving 976 494 patients, were analysed. The OD regimen demonstrated significantly higher adherence and persistence (P <
.05) than the BID regimen in most outcomes. Adherence favoured OD in 53.1% of cases, while only 12.2% favoured BID. Similarly, persistence was higher with the OD regimen in 67.7% of cases compared to 14.9% for the BID regimen. These results remained consistent over time
nevertheless, variations were observed depending on the specific DOAC molecules. CONCLUSION: Adherence and persistence of treatment with DOACs in patients with NVAF were greater for the OD than for the BID regimen.